Increased Secretion of Endogenous GH after Treatment with an Intranasal GH-releasing Peptide-2 Spray Does Not Promote Growth in Short Children with GH Deficiency

Abstract

We investigated whether treatment with an intranasal GH-releasing peptide (GHRP)-2 spray, which acts as a potent GH secretagogue that stimulates endogenous GH secretion, promotes growth in patients with GH deficiency (GHD). This study involved 126 prepubertal short children (81 males, 45 females) with a height SD score of -2 SD or less, who had been diagnosed as having GHD based on GH stimulation tests, and in whom the serum GH concentrations increased up to 9 ng/ml after preliminary administration of an intranasal GHRP-2 spray. The subjects included in this study were divided into 3 groups by use of a double-blind method; that is 44 were placed into the placebo group (P group: 30 males, 14 females), 41 were placed into the GHRP-2 low dose group (L group: 25 males, 16 females), and 41 were placed into the GHRP-2 high dose group (H group: 26 males, 15 females). Those with a body wt of less than 20 kg were administered a placebo (P group), 50 μg of GHRP-2 (L group) or 100 μg of GHRP-2 (H group), and those with a body wt of 20 kg or more were administered a placebo (P group), 100 µg of GHRP-2 (L group) or 200 µg of GHRP-2 (H group) twice daily (morning and evening) for 48 continuous wk. Age and height SD scores at baseline were not significantly different among the three groups: 7.5 yr old and -2.26 SD in the P group, 7.3 yr old and -2.38 SD in the L group, and 7.5 yr old and -2.27 SD in the H group. Of the 126 subjects, 44, 40 and 40 subjects in the P, L and H groups, respectively, completed the 48 continuous wk of treatment. The changes in the mean height SD scores (mean growth rate) after 48 wk of treatment in the P, L and H groups were 0.07 SD, 0.03 SD, and 0.02 SD, respectively, and thus no significant differences was observed among the 3 groups. Also no significant changes in blood IGF-I levels at baseline or after 48 wk of treatment were observed among the 3 groups. This study revealed that in patients with GHD, an increase in endogenous GH secretion as a result of treatment with GHRP-2 does not promote growth. It is speculated that the area under the curve of serum GH concentration by GHRP-2 spray is too small to produce biological effects. In conclusion, it was demonstrated that growth cannot be promoted by a transient increase in endogenous GH secretion.

Keywords: GH deficiency; endogenous GH; intranasal GHRP-2 spray.

Fig. 1.

Mean peak serum GH concentrations after administration of the GHRP-2 nasal spray at the start of treatment and at 24 wk and 48 wk of treatment in three groups of GHRP-2 doses. Numbers of subjects are shown in parentheses. *p < 0.05.

Fig. 2.

Mean serum IGF-I concentrations before the GHRP-2 treatment and 48 wk after treatment in three groups of GHRP-2 doses. Vertical bars indicate the SD. Numbers of subjects are shown in parentheses.

Fig. 3.

Growth velocity before and during the 48 wk of treatment. Vertical bars indicate the SD. Numbers of subjects are shown in parentheses.

Fig. 4.

Mean serum concentration after administration of nasal spray and subcutaneous injection of GH.